1. Field of the Invention
This invention relates to the synthesis of aspirin peroxide. 2. Description of the Prior Art
2,2'-Diacetoxy-dibenzoyl-peroxide, commonly called aspirin peroxide, is a member of the chemical class of compounds known as acyl-salicyloyl peroxides described in Beilstein's Handbuch Der Organischen Chemie, Aweites Erganzungswerk, Die-literatur von 1920-1929 umfassend; Unfelder and Vanino, Pharm. Zeitung 47, 847 (1902); and Vanino, Herzer, Ar. 441(1924). In Beilstein the preparation of 2,2'-diacetoxy-dibenzoyl-peroxide is described by reacting 2-acetyl-salicyloyl chloride with aqueous 30% (w/w) hydrogen peroxide in acetone using pyridine as the organic base. The resulting product is recrystallized from benzene and has a m.p. of 109.degree.-110.degree. C. with decomposition.
U.S. Pat. No. 4,364,940 describes aspirin peroxide as having anti-bacterial activity and being useful in the treatment of acne. The process of making aspirin peroxide involves the use of a reaction mixture of 2-acetyl-salicyloyl chloride, aqueous 30% hydrogen peroxide in acetone, anhydrous sodium sulfate and sodium bicarbonate at a reaction temperature of 0.degree. C.
It is well recognized by scientists in this field that organic peroxides, and particularly aspirin peroxide, are potentially hazardous compounds due to their thermal and mechanical instability. For example, the use of acetone as a reaction medium is rather undesirable due to the possible formation of trace amounts of 2,2-dihydroperoxy propane which is shock sensitive. In addition, during the removal of acetone for the purpose of concentrating the organic peroxide, pockets of concentrated acetone solutions are formed containing peroxide impurities which are inherently unstable towards rapid decomposition and explosion. In any process for the synthesis of these materials this potential hazard must be acknowledged in order to provide a method which is both chemically efficient in terms of yield and quality of products, as well as technologically practical and feasible in terms of handling and operations. Futhermore, conventional synthetic methods for the preparation of organic peroxides, such as dibenzoyl peroxide, are not suitable for the synthesis of aspirin peroxide for the reasons that hydrolysis of the 2-acetoxy group in aspirin peroxide would occur resulting in hazardous, potentially detonating conditions in addition to low yields and the presence of unacceptably high levels of impurities.
A safe, efficient synthetic method for the preparation of 2,2'-diacetoxy-dibenzoyl-peroxide has been discovered in which the hazards associated with thermal and mechanical instability of the reactants and product are minimized resulting in a high product yield of from 36 to 45% and of at least 95% purity.